The objective of this contract is to understand the human mucosal immune response generated by infection or vaccination with enteric bacteria and viruses. This information is needed in order to develop effective vaccination strategies against enteric pathogens. The contractor will employ studies of human adult volunteers to accomplish the objectives of the contract. Individuals will be challenged with genetically weakened (attenuated) or wild-type Escherichia coli, Salmonella species, Shigella species, Vibrio cholerae, Campylobacter species, Helicobacter pylori, rotavirus, other enteric viruses, or other appropriate organisms. Their immune response to such challenge will be extensively characterized in order to identify those aspects of the immune response that correlate with protection from challenge by wild-type organisms. Once identified, further efforts will be made through iterative methodology to maximize that protective aspect of the immune response through the use of various adjuvants, delivery systems, dosing schedules or other methods. The contractor will recruit adult volunteers from the Baltimore/Washington metropolitan community, screen them for appropriate immune status, instruct them about the nature of the study and its objectives, perform the studies on an isolation ward in the hospital or in out-patients when appropriate, and provide the necessary follow-up and treatment for all volunteers. It is further intended that the contractor will interact effectively and frequently with a second contractor working on equivalent studies of respiratory pathogens (Baylor College of Medicine, N01-AI-65298). It is anticipated that synergistic effects will be achieved by these two groups in the furthering of our understanding of the human mucosal immune response. Such a result will likely benefit studies of diseases other than those associated with the digestive or respiratory systems. It is anticipated that these studies will lead to more effective vaccine strategies against a large number of infectious diseases.